Post-stroke changes in brain structure and function can both influence acute upper limb function and subsequent recovery

• Upper limb motor impairment is a prevalent consequence of stroke. • Enhancing outcomes necessitates an understanding of the mechanisms underlying recovery. • Both brain structure and brain function offer valuable prognostic insights. • Intra-hemispheric connectivity is associated with initial motor impairment. • Inter-hemispheric connectivity is associated with subsequent motor recovery. Improving outcomes after stroke depends on understanding both the causes of initial function/impairment and the mechanisms of recovery. Recovery in patients with initially low function/high impairment is variable, suggesting the factors relating to initial function/impairment are different to the factors important for subsequent recovery. Here we aimed to determine the contribution of altered brain structure and function to initial severity and subsequent recovery of the upper limb post-stroke. The Nine-Hole Peg Test was recorded in week 1 and one-month post-stroke and used to divide 36 S patients (18 females, age: M = 66.56 years) into those with high/low initial function and high/low subsequent recovery. We determined differences in week 1 brain structure (Magnetic Resonance Imaging) and function (Magnetoencephalography, tactile stimulation) between high/low patients for both initial function and subsequent recovery. Lastly, we examined the relative contribution of changes in brain structure and function to recovery in patients with low levels of initial function. Low initial function and low subsequent recovery are related to lower sensorimotor β power and greater lesion-induced disconnection of contralateral [ipsilesional] white-matter motor projection connections. Moreover, differences in intra-hemispheric connectivity (structural and functional) are unique to initial motor function, while differences in inter-hemispheric connectivity (structural and functional) are unique to subsequent motor recovery. Function-related and recovery-related differences in brain function and structure after stroke are related, yet not identical. Separating out the factors that contribute to each process is key to identifying potential therapeutic targets for improving outcomes.